Cancer is one of the leading causes of death in the United States. Cancerous tumors result when a cell escapes from its normal growth regulatory mechanisms and proliferates in an uncontrolled manner. Tumor cells can metastasize to secondary sites if treatment of the primary tumor is either not complete or not initiated before substantial progression of the disease. Early diagnosis and effective treatment of tumors is, therefore, essential for survival.
Cancer involves the replication of populations of abnormal cells that have gained competitive advantage over normal cells through the alteration of regulatory genes. Regulatory genes can be broadly classified into “oncogenes” which, when activated or overexpressed, promote unregulated cell proliferation, and “tumor suppressor genes,” which when inactivated or underexpressed, fail to prevent abnormal cell proliferation. Loss of function or inactivation of tumor suppressor genes is thought to play a central role in the initiation and progression of a significant number of human cancers.
Currently, breast and/or ovarian cancer are treated by surgery, radiation therapy, chemotherapy, targeted therapy, and hormonal therapy. To date, targeted therapies include trastuzumab and lapatinib, which target breast cancers that have increased HER2 receptors (HER2-positive). Bevacizumab targets the new blood vessels that feed cancer cells. Hormonal therapy blocks the ability of the hormone estrogen to stimulate the growth of breast cancer cells. Aromatase inhibitors, selective estrogen receptor modulators (SERMs), and estrogen-receptor down regulators are all different types of hormonal therapy currently available to breast cancer patients.
There are still many unsolved problems, disadvantages, and/or shortcomings that currently exist in the prevention and/or treatment of ovarian and/or breast cancer. Target therapies only work for HER2 positive breast cancers. However, only 15 to 20% of women with breast cancer have HER2-positive tumors. Hormonal therapy is an option for anyone with hormone receptor positive breast cancer. About 60% of breast cancers are hormone receptor positive. However, there are several side effects with hormonal therapy, including uterine cancer and weakening of the bones. Additionally, the side effects of current therapeutic regimens are treated as they appear in patients.
Additionally, mutations in one known tumor suppressor gene, breast cancer susceptibility to gene one (BRCA1), contribute in essentially all cases to inherited susceptibility to ovarian and breast cancers. Additionally, BRCA1 expression levels are reduced or undetectable in the tumor cells of sporadic breast cancers. In view of the importance of tumor suppressor molecules in the detection and treatment of cancer, and the known correlation of the tumor suppressor BRCA1 with breast and ovarian cancers, there exists a need to identify compounds that influence the level or activity of BRCA1.
Therefore, it would be beneficial to have a compound and method of use that will increase BRCA1 expression so as to delay and/or inhibit the onset of tumors. Such compounds and methods of use would be significant change in the treatment options for breast and ovarian cancer, as well as other cancers.